DIALYSIS? HEMOPERFUSION? What’s up with enhanced elimination of drugs? - PowerPoint PPT Presentation

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DIALYSIS? HEMOPERFUSION? What’s up with enhanced elimination of drugs?

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DIALYSIS? HEMOPERFUSION? What s up with enhanced elimination of drugs? Kent R. Olson, MD Medical Director - SF Division California Poison Control System – PowerPoint PPT presentation

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Title: DIALYSIS? HEMOPERFUSION? What’s up with enhanced elimination of drugs?


1
DIALYSIS? HEMOPERFUSION?Whats up with enhanced
elimination of drugs?
  • Kent R. Olson, MD
  • Medical Director - SF Division
  • California Poison Control System

2
Case study
  • A 30 year old man accidentally drank 3 ounces
    of CAMPHORATED OIL, mistaking it for castor oil.
  • He vomited and later developed seizures and
    hypotension.
  • After 2 hours of hemoperfusion he began to
    awaken, and he subsequently recovered fully.

3
Hemoperfusion
ARTERY or VEIN
VEIN
Blood from patient
Return to patient
Uses hemodialysis machine - but runs blood
directly through a charcoal- or
sorbent-containing filter
4
Case, continued . . .
  • The plasma camphor level before hemoperfusion was
    1.7 mcg/mL
  • Extraction of camphor by the machine was 99
  • However, no measurement of the total amount of
    camphor removed
  • Probably less than 1 of the18 gram dose was
    removed !!

5
What happened?
  • Triumph of the anecdotal case
  • I did such and so
  • the patient got better
  • it must have been the SUCH and SO!
  • But
  • the volume of distribution of camphor is HUGE
  • and, the patient would likely have gotten better
    anyway, despite the hemoperfusion

6
Enhanced drug elimination
  • Who needs it?
  • Will it work?
  • Whats the best technique?

7
Its not used very often
  • 1995 AAPCC data - 2 million poisonings
  • Urine alkalinization used in 0.35
  • Hemodialysis used in 0.04
  • Hemoperfusion used in 0.0003

8
Who needs it?
  • Critically ill despite supportive care
  • eg, phenobarb OD w/ intractable shock
  • Known lethal dose or blood level
  • eg, salicylate methanol / ethylene glycol
    theophylline paraquat?
  • Usual route of elimination impaired
  • eg, lithium OD in oliguric patient
  • Risk of prolonged coma
  • eg, phenobarbital OD w/ level of 200

9
Will it work?
  • Volume of distribution
  • is the drug accessible?
  • how big a volume to clear?
  • Clearance (CL)
  • does the method efficiently cleanse the blood?
  • what is the intrinsic clearance?

10
Volume of distribution (Vd)
  • A calculated number - not real amt. of drug /
    plasma conc. mg/kg / mg/L L/kg
  • Total body water 0.7 L/kg or 50 L
  • ECF 0.25 L/kg or about 15 L in adult
  • Blood or plasma 0.07 L/kg or 5 L

11
Vd for some common drugs
  • Large Vd
  • camphor
  • antidepressants
  • digoxin
  • opioids
  • phencyclidine
  • phenothiazines
  • Small Vd
  • alcohols
  • lithium
  • phenobarbital
  • phenytoin
  • salicylate
  • valproic acid

12
But they reported the CLEARANCE was really good
- - - 200 mL/min . . .
  • CL flow rate x extraction ratioeg, dialysis
    rate 250 mL/min if extraction is 80, Cl 200
    mL/min
  • But Cl is expressed in mL/min . . . NOT mg/min or
    gm/hr or tons/day
  • Total drug elimination depends on drug
    concentration
  • mcg/mL x mL/min mg/min

13
Example amitriptyline OD
  • 60 kg man ingests 100 x 25 mg Elavil tabs
  • Vd 40 L/kg or 2400 L
  • Est. Cp 2500 mg / 2400 L 1 mcg/mL
  • Hemoperfusion with CL of 200 mL/min
  • Drug removal 200 mL/min x 1 mcg/mL 200
    mcg/min or 0.2 mg/min or 0.5 per hour

14
Two drugs with the same CL
  • Dialysis CL Vd Fraction eliminated in
    60 min of dialysis
  • 200 mL/min 500 L 1
  • 200 mL/min 50 L 17

T½ 0.693 Vd / CL
15
What is the intrinsic CL?
  • If intrinsic (or endogenous) CL is large, an
    enhanced removal method may not add much to total
    CL
  • examples of HIGH endogenous CL lidocaine,
    opioids, TCAs, many beta-blockers
  • examples of LOW endogenous CL alcohols,
    atenolol, lithium, salicylate, phenytoin,
    theophylline
  • General rule method should increase total CL by
    at least 30

16
Summary of desired kinetics
  • Small volume of distribution
  • Vd less than 1 L/kg
  • Low endogenous CL
  • less than 4 mL/min/kg
  • Single-compartment kinetics
  • rapid equilibration between blood and tissues
  • avoid problem of rebound in blood levels

17
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18
Which method?
  • Urinary pH manipulation
  • Peritoneal dialysis
  • Hemodialysis
  • Hemoperfusion
  • Mulitple dose activated charcoal
  • Continuous hemofiltration

19
Urinary pH manipulation
  • Alkaline diuresis
  • traps weak acids in alkaline urine
  • useful for salicylates, phenobarbital,
    chlorpropamide
  • risk of fluid overload
  • Acid diuresis
  • traps weak bases
  • may enhance elimination of amphetamines
  • TOO RISKY - may worsen myoglobinuric RF

20
Peritoneal dialysis
  • Theoretically useful if drug is
  • water soluble
  • small (MW lt500)
  • not highly protein bound
  • not so bad you dont mind waiting . . . TOO SLOW
  • Rarely performed unless its the only available
    method

21
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22
Hemodialysis
  • Can be arteriovenous or veno-venous (double-lumen
    catheter)
  • Requires anticoagulation
  • Best if drug is
  • water-soluble
  • small (MW lt500)
  • not highly protein bound
  • Also good for correcting fluid electrolyte
    abnormalities

23
Hemodialysis, continued . . .
  • Newer machines have higher flow rates, better
    extraction ratios
  • Note DONT use the REDY system - these portable
    HD units have very limited volume dialysate which
    is recycled, and CL may be very poor

24
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25
Charcoal hemoperfusion
  • Uses same vascular access and dialysis pumps
  • Greater anticoagulation required
  • Saturation of charcoal limits duration
  • But, it is not dependent on drug size, water
    solubility or protein binding - as long as drug
    binds to charcoal
  • Can be used in series with dialysis

26
Multiple dose oral charcoal - gut dialysis
  • Charcoal slurry along the entire intestinal tract
  • Large surface area for adsorption of drug
    diffusing across intestinal epithelium from
    capillaries
  • Useful if drug likes AC, small Vd, low protein
    binding
  • Clinical benefit unproven

27
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28
Continuous hemofiltration
  • Plasma moves across semipermeable membrane under
    hydrostatic pressure
  • No dialysate
  • Solutes follow the plasma water - size up to MW
    10,000-40,000
  • CL lower than HD or HP, but it can be performed
    24 hrs/day

29
Drug Preferred Method
  • Carbamazepine HP
  • Ethylene glycol HD
  • Lithium HD
  • Methanol HD
  • Methotrexate HF
  • Phenobarbital HP
  • Procainamide HF
  • Salicylate HD or HP
  • Theophylline HP or HD
  • Valproic acid HD or HP

30
Salicylate poisoning
  • Indications for dialysis
  • severe metabolic acidosis
  • serum level gt 100 mg/dL (acute OD)
  • level gt 60 mg/dL (elderly, chronic OD)
  • Note
  • check units!! (mg/dL vs mg/L)
  • alkalinize serum and urine
  • dialysis preferred can correct electrolyte and
    fluid abnormalities

31
Theophylline poisoning
  • Indications for dialysis
  • serum level gt 100 mg/L (acute OD)
  • level gt 60-80 mg/L? (chronic)
  • seizures
  • Notes
  • HP or high-flux HD
  • Control Sz w/ phenobarbital
  • Rx hypotension w/ beta blockers

32
Methanol, Ethylene Glycol
  • Indications for dialysis
  • elevated level gt 50 mg/dL
  • severe acidosis
  • increased osmolal gap gt 10-15 mmol/L
  • Notes
  • HD only - not adsorbed to AC
  • give blocking drug (EtOH, 4-MP) - Note need to
    increase dosing during dialysis

33
Phenobarbital
  • Indications for dialysis
  • level gt 190-200 mg/L
  • failure of supportive care (ie, intractable
    hypotension)
  • Notes
  • rarely seen anymore
  • HP gt HD
  • repeated dose AC shortens half-life but not
    length of coma

34
Lithium
  • Indications for dialysis
  • serum level gt 6? 8? 10? (acute OD)
  • level gt 4 ? (chronic)
  • level 2.5-4 with severe Sx?
  • Notes
  • 2-compartment model, very slow redistribution
    from tissues
  • patients rarely get quick improvement
  • difficult to evaluate need and benefit
  • IV saline diuresis may be nearly as effective

35
Lithium
36
Estimate for Lithium
  • Usual renal Cl 25-35 mL/min
  • Hemodialysis adds 100-150 mL/min
  • But only for 3-4 hours at a time
  • Rebound between dialysis sessions
  • CVVH adds 20-35 mL/min
  • But can be provided continuously
  • Volume cleared 50L/dayvs 36 L/day w/ 4 hours
    of HD
  • No rebound

37
Remember
  • Consider pharmacokinetics and known behavior of
    the drug
  • What clinical evidence is there for benefit with
    enhanced removal?
  • Most patients will get better anyway
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